This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the first project, Dr. Kirn-Safran proposes to define precisely the structural and functional roles that perlecan (Pln) and its associated heparan sulfate (HS) proteoglycan chains play in cartilage biology. HS proteoglycans have recently emerged as key regulators of cartilage biology and play critical roles during embryonic development, in maintenance of cartilage structures in the adult organism, and in regrowth of damaged cartilage resulting from age, osteoarthritis or injury. Using a combination of in vitro chondrogenesis models and mice harboring mutations in Pln or HS biosynthetic enzymes, Dr. Kirn-Safran et al. will address the hypothesis that Pln and heparanase I are essential players in normal chondrogenesis and cartilage healing, and that their complex roles in these processes are associated with specialized functions encrypted within the various domains and require the presence and turnover of HS. Dr. Kirn-Safran is mentored by Dr. Duncan.